15-49462547-C-G

Variant names:

• chr15-49462547-C-G
• rs7167041
• NM_152647.3:c.1012+45664G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152647.3(FAM227B):​c.1012+45664G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,986 control chromosomes in the GnomAD database, including 8,722 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8722 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 2 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FGF7 (HGNC:3685): (fibroblast growth factor 7) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1012+45664G>C		intron	N/A	NP_689860.2	Q96M60-1
	FGF7	NM_002009.4	MANE Select	c.287-20604C>G		intron	N/A	NP_002000.1	P21781-1
	FAM227B	NM_001330293.2		c.911-39833G>C		intron	N/A	NP_001317222.1	Q96M60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1012+45664G>C		intron	N/A	ENSP00000299338.6	Q96M60-1
	FGF7	ENST00000267843.9	TSL:1 MANE Select	c.287-20604C>G		intron	N/A	ENSP00000267843.4	P21781-1
	FAM227B	ENST00000561064.5	TSL:1	c.911-39833G>C		intron	N/A	ENSP00000453028.1	Q96M60-2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49240 AN: 151868 Hom.: 8710 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 49297 AN: 151986 Hom.: 8722 Cov.: 32 AF XY: 0.323 AC XY: 23967 AN XY: 74284

African (AFR) AF: 0.452 AC: 18734 AN: 41438

American (AMR) AF: 0.376 AC: 5743 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1965 AN: 5156

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4822

European-Finnish (FIN) AF: 0.244 AC: 2575 AN: 10568

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17227 AN: 67964

Other (OTH) AF: 0.321 AC: 677 AN: 2112

Alfa AF: 0.272 Hom.: 723

Bravo AF: 0.343

Asia WGS AF: 0.326 AC: 1135 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7167041; hg19: chr15-49754744;